Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion

Simona Parisse; Alessandra Gianoncelli; Gloria Isani; Francesco Luigi Gambaro; Giulia Andreani; Emil Malucelli; Giuliana Aquilanti; Ilaria Carlomagno; Raffaella Carletti; Monica Mischitelli; Flaminia Ferri; Veronica Paterna; Quirino Lai; Gianluca Mennini; Fabio Melandro; Cira Di Gioia; Massimo Rossi; Stefano Iotti; Michela Fratini; Stefano Ginanni Corradini

doi:10.3390/nu15112626

Nutrients (Jun 2023)

Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion

Simona Parisse,
Alessandra Gianoncelli,
Gloria Isani,
Francesco Luigi Gambaro,
Giulia Andreani,
Emil Malucelli,
Giuliana Aquilanti,
Ilaria Carlomagno,
Raffaella Carletti,
Monica Mischitelli,
Flaminia Ferri,
Veronica Paterna,
Quirino Lai,
Gianluca Mennini,
Fabio Melandro,
Cira Di Gioia,
Massimo Rossi,
Stefano Iotti,
Michela Fratini,
Stefano Ginanni Corradini

Affiliations

Simona Parisse: Department of Translational and Precision Medicine, “Sapienza” University of Rome, Viale dell’Università 37, 00185 Rome, Italy
Alessandra Gianoncelli: Elettra-Sincrotrone Trieste, Strada Statale 14 km 163,5 in AREA Science Park, Basovizza, 34149 Trieste, Italy
Gloria Isani: Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, Via Tolara di Sopra 50, 50055-Ozzano dell’Emilia, 40064 Bologna, Italy
Francesco Luigi Gambaro: Department of Radiological Sciences, Oncology and Pathological Anatomy, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Giulia Andreani: Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, Via Tolara di Sopra 50, 50055-Ozzano dell’Emilia, 40064 Bologna, Italy
Emil Malucelli: Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy
Giuliana Aquilanti: Elettra-Sincrotrone Trieste, Strada Statale 14 km 163,5 in AREA Science Park, Basovizza, 34149 Trieste, Italy
Ilaria Carlomagno: Elettra-Sincrotrone Trieste, Strada Statale 14 km 163,5 in AREA Science Park, Basovizza, 34149 Trieste, Italy
Raffaella Carletti: Department of Radiological Sciences, Oncology and Pathological Anatomy, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Monica Mischitelli: Department of Translational and Precision Medicine, “Sapienza” University of Rome, Viale dell’Università 37, 00185 Rome, Italy
Flaminia Ferri: Department of Translational and Precision Medicine, “Sapienza” University of Rome, Viale dell’Università 37, 00185 Rome, Italy
Veronica Paterna: Department of Translational and Precision Medicine, “Sapienza” University of Rome, Viale dell’Università 37, 00185 Rome, Italy
Quirino Lai: General Surgery and Organ Transplantation Unit, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Gianluca Mennini: General Surgery and Organ Transplantation Unit, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Fabio Melandro: General Surgery and Organ Transplantation Unit, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Cira Di Gioia: Department of Radiological Sciences, Oncology and Pathological Anatomy, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Massimo Rossi: General Surgery and Organ Transplantation Unit, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Stefano Iotti: Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy
Michela Fratini: CNR-Institute of Nanotechnology c/o Physics Department, Sapienza University of Rome, Piazzale Aldo Moro 7, 00185 Rome, Italy
Stefano Ginanni Corradini: Department of Translational and Precision Medicine, “Sapienza” University of Rome, Viale dell’Università 37, 00185 Rome, Italy

DOI: https://doi.org/10.3390/nu15112626
Journal volume & issue: Vol. 15, no. 11
p. 2626

Abstract

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We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation, we measured the magnesium content in liver tissue in 27 cirrhotic patients (CIRs) and 16 deceased donors with healthy liver (CTRLs) by atomic absorption spectrometry and within hepatocytes of 15 CIRs using synchrotron-based X-ray fluorescence microscopy. In 31 CIRs and 10 CTRLs, we evaluated the immunohistochemical expression in hepatocytes of the transient receptor potential melastatin 7 (TRPM7), a magnesium influx chanzyme also involved in inflammation. CIRs showed a lower hepatic magnesium content (117.2 (IQR 110.5–132.9) vs. 162.8 (IQR 155.9–169.8) μg/g; p p < 0.001) than CTRLs. In CIRs, MELDNa and serum AST at transplant correlated: (a) inversely with the magnesium content both in liver tissue and hepatocytes; and (b) directly with the percentage of hepatocytes stained intensely for TRPM7. The latter also directly correlated with the worsening of MELDNa at transplant compared to waitlisting. Magnesium depletion and overexpression of its influx chanzyme TRPM7 in hepatocytes are associated with severity of hepatocyte injury and prognosis in cirrhosis. These data represent the pathophysiological basis for a possible beneficial effect of magnesium supplementation in cirrhotic patients.

Published in Nutrients

ISSN: 2072-6643 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Technology: Home economics: Nutrition. Foods and food supply
Website: https://www.mdpi.com/journal/nutrients

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